N6-methyladenine DNA modification in Drosophila.

DNA N(6)-methyladenine (6mA) modification is commonly found in microbial genomes and plays important functions in regulating numerous biological processes in bacteria. However, whether 6mA occurs and what its potential roles are in higher-eukaryote cells remain unknown. Here, we show that 6mA is present in Drosophila genome and that the 6mA modification is dynamic and is regulated by the Drosophila Tet homolog, DNA 6mA demethylase (DMAD), during embryogenesis. Importantly, our biochemical assays demonstrate that DMAD directly catalyzes 6mA demethylation in vitro. Further genetic and sequencing analyses reveal that DMAD is essential for development and that DMAD removes 6mA primarily from transposon regions, which correlates with transposon suppression in Drosophila ovary. Collectively, we uncover a DNA modification in Drosophila and describe a potential role of the DMAD-6mA regulatory axis in controlling development in higher eukaryotes.

Streptomyces umbrella toxin particles block hyphal growth of competing species.

Streptomyces are a genus of ubiquitous soil bacteria from which the majority of clinically utilized antibiotics derive1. The production of these antibacterial molecules reflects the relentless competition Streptomyces engage in with other bacteria, including other Streptomyces species1,2. Here we show that in addition to small-molecule antibiotics, Streptomyces produce and secrete antibacterial protein complexes that feature a large, degenerate repeat-containing polymorphic toxin protein. A cryo-electron microscopy structure of these particles reveals an extended stalk topped by a ringed crown comprising the toxin repeats scaffolding five lectin-tipped spokes, which led us to name them umbrella particles. Streptomyces coelicolor encodes three umbrella particles with distinct toxin and lectin composition. Notably, supernatant containing these toxins specifically and potently inhibits the growth of select Streptomyces species from among a diverse collection of bacteria screened. For one target, Streptomyces griseus, inhibition relies on a single toxin and that intoxication manifests as rapid cessation of vegetative hyphal growth. Our data show that Streptomyces umbrella particles mediate competition among vegetative mycelia of related species, a function distinct from small-molecule antibiotics, which are produced at the onset of reproductive growth and act broadly3,4. Sequence analyses suggest that this role of umbrella particles extends beyond Streptomyces, as we identified umbrella loci in nearly 1,000 species across Actinobacteria.

Epitranscriptional m6A modification of rRNA negatively impacts translation and host colonization in Staphylococcus aureus.

Macrolides, lincosamides, and streptogramin B (MLS) are structurally distinct molecules that are among the safest antibiotics for prophylactic use and for the treatment of bacterial infections. The family of erythromycin resistance methyltransferases (Erm) invariantly install either one or two methyl groups onto the N6,6-adenosine of 2058 nucleotide (m6A2058) of the bacterial 23S rRNA, leading to bacterial cross-resistance to all MLS antibiotics. Despite extensive structural studies on the mechanism of Erm-mediated MLS resistance, how the m6A epitranscriptomic mark affects ribosome function and bacterial physiology is not well understood. Here, we show that Staphylococcus aureus cells harboring m6A2058 ribosomes are outcompeted by cells carrying unmodified ribosomes during infections and are severely impaired in colonization in the absence of an unmodified counterpart. The competitive advantage of m6A2058 ribosomes is manifested only upon antibiotic challenge. Using ribosome profiling (Ribo-Seq) and a dual-fluorescence reporter to measure ribosome occupancy and translational fidelity, we found that specific genes involved in host interactions, metabolism, and information processing are disproportionally deregulated in mRNA translation. This dysregulation is linked to a substantial reduction in translational capacity and fidelity in m6A2058 ribosomes. These findings point to a general "inefficient translation" mechanism of trade-offs associated with multidrug-resistant ribosomes.

Flanking strand separation activity of RecA nucleoprotein filaments in DNA strand exchange reactions.

The recombinase RecA/Rad51 ATPase family proteins catalyze paramount DNA strand exchange reactions that are critically involved in maintaining genome integrity. However, it remains unclear how DNA strand exchange proceeds when encountering RecA-free defects in recombinase nucleoprotein filaments. Herein, by designing a series of unique substrates (e.g. truncated or conjugated incoming single-stranded DNA, and extended donor double-stranded DNA) and developing a two-color alternating excitation-modified single-molecule real-time fluorescence imaging assay, we resolve the two key steps (donor strand separation and new base-pair formation) that are usually inseparable during the reaction, revealing a novel long-range flanking strand separation activity of synaptic RecA nucleoprotein filaments. We further evaluate the kinetics and free energetics of strand exchange reactions mediated by various substrates, and elucidate the mechanism of flanking strand separation. Based on these findings, we propose a potential fundamental molecular model involved in flanking strand separation, which provides new insights into strand exchange mechanism and homologous recombination.

A combination of conserved and diverged responses underlies Theobroma cacao's defense response to Phytophthora palmivora.

BACKGROUND: Plants have complex and dynamic immune systems that have evolved to resist pathogens. Humans have worked to enhance these defenses in crops through breeding. However, many crops harbor only a fraction of the genetic diversity present in wild relatives. Increased utilization of diverse germplasm to search for desirable traits, such as disease resistance, is therefore a valuable step towards breeding crops that are adapted to both current and emerging threats. Here, we examine diversity of defense responses across four populations of the long-generation tree crop Theobroma cacao L., as well as four non-cacao Theobroma species, with the goal of identifying genetic elements essential for protection against the oomycete pathogen Phytophthora palmivora. RESULTS: We began by creating a new, highly contiguous genome assembly for the P. palmivora-resistant genotype SCA 6 (Additional file 1: Tables S1-S5), deposited in GenBank under accessions CP139290-CP139299. We then used this high-quality assembly to combine RNA and whole-genome sequencing data to discover several genes and pathways associated with resistance. Many of these are unique, i.e., differentially regulated in only one of the four populations (diverged 40 k-900 k generations). Among the pathways shared across all populations is phenylpropanoid biosynthesis, a metabolic pathway with well-documented roles in plant defense. One gene in this pathway, caffeoyl shikimate esterase (CSE), was upregulated across all four populations following pathogen treatment, indicating its broad importance for cacao's defense response. Further experimental evidence suggests this gene hydrolyzes caffeoyl shikimate to create caffeic acid, an antimicrobial compound and known inhibitor of Phytophthora spp. CONCLUSIONS: Our results indicate most expression variation associated with resistance is unique to populations. Moreover, our findings demonstrate the value of using a broad sample of evolutionarily diverged populations for revealing the genetic bases of cacao resistance to P. palmivora. This approach has promise for further revealing and harnessing valuable genetic resources in this and other long-generation plants.

The Warburg effect drives cachectic states in patients with pancreatobiliary adenocarcinoma.

We have studied whether the Warburg effect (uncontrolled glycolysis) in pancreatobiliary adenocarcinoma triggers cachexia in the patient. After 74 pancreatobiliary adenocarcinomas were removed by surgery, their glucose transporter-1 and four glycolytic enzymes were quantified using Western blotting. Based on the resulting data, the adenocarcinomas were equally divided into a group of low glycolysis (LG) and a group of high glycolysis (HG). Energy homeostasis was assessed in these cancer patients and in 74 non-cancer controls, using serum albumin and C-reactive protein and morphometrical analysis of abdominal skeletal muscle and fat on computed tomography scans. Some removed adenocarcinomas were transplanted in nude mice to see their impacts on host energy homeostasis. Separately, nude mice carrying tumor grafts of MiaPaCa-2 pancreatic adenocarcinoma cells were treated with the glycolytic inhibitor 3-bromopyruvate and with emodin that inhibited glycolysis by decreasing hypoxia-inducible factor-1α. Adenocarcinomas in both group LG and group HG impaired energy homeostasis in the cancer patients, compared to the non-cancer reference. The impaired energy homeostasis induced by the adenocarcinomas in group HG was more pronounced than that by the adenocarcinomas in group LG. When original adenocarcinomas were grown in nude mice, their glycolytic abilities determined the levels of hepatic gluconeogenesis, skeletal muscle proteolysis, adipose-tissue lipolysis, and weight loss in the mice. When MiaPaCa-2 cells were grown as tumors in nude mice, 3-bromopyruvate and emodin decreased tumor-induced glycolysis and cachexia, with the best effects being seen when the drugs were administered in combination. In conclusion, the Warburg effect in pancreatobiliary adenocarcinoma triggers cancer cachexia.

ZNF148 inhibits HBV replication by downregulating RXRα transcription.

BACKGROUND: Progressive hepatitis B virus (HBV) infection can result in cirrhosis, hepatocellular cancer, and chronic hepatitis. While antiviral drugs that are now on the market are efficient in controlling HBV infection, finding a functional cure is still quite difficult. Identifying host factors involved in regulating the HBV life cycle will contribute to the development of new antiviral strategies. Zinc finger proteins have a significant function in HBV replication, according to earlier studies. Zinc finger protein 148 (ZNF148), a zinc finger transcription factor, regulates the expression of various genes by specifically binding to GC-rich sequences within promoter regions. The function of ZNF148 in HBV replication was investigated in this study. METHODS: HepG2-Na+/taurocholate cotransporting polypeptide (HepG2-NTCP) cells and Huh7 cells were used to evaluate the function of ZNF148 in vitro. Northern blotting and real-time PCR were used to quantify the amount of viral RNA. Southern blotting and real-time PCR were used to quantify the amount of viral DNA. Viral protein levels were elevated, according to the Western blot results. Dual-luciferase reporter assays were used to examine the transcriptional activity of viral promoters. ZNF148's impact on HBV in vivo was investigated using an established rcccDNA mouse model. RESULTS: ZNF148 overexpression significantly decreased the levels of HBV RNAs and HBV core DNA in HBV-infected HepG2-NTCP cells and Huh7 cells expressing prcccDNA. Silencing ZNF148 exhibited the opposite effects in both cell lines. Furthermore, ZNF148 inhibited the activity of HBV ENII/Cp and the transcriptional activity of cccDNA. Mechanistic studies revealed that ZNF148 attenuated retinoid X receptor alpha (RXRα) expression by binding to the RXRα promoter sequence. RXRα binding site mutation or RXRα overexpression abolished the suppressive effect of ZNF148 on HBV replication. The inhibitory effect of ZNF148 was also observed in the rcccDNA mouse model. CONCLUSIONS: ZNF148 inhibited HBV replication by downregulating RXRα transcription. Our findings reveal that ZNF148 may be a new target for anti-HBV strategies.

Association of health behaviors in life's essential 8 and hypertension in adolescents: a cross-sectional study from the NHANES database.

BACKGROUND: Hypertension is a common condition during adolescence with increasing prevalence globally, alongside the epidemic of unhealthy lifestyles and obesity. Health behaviors have been shown to be associated with hypertension risk in adults. Life's essential 8 (LE8), as a comprehensive indicator to evaluate cardiovascular health (CVH), includes 4 health factors and 4 health behaviors. This study aims to evaluate the association between health behaviors defined in LE8 and hypertension among adolescents. METHODS: Data of this study were extracted from the National Health and Nutrition Examination Surveys (NHANES) 2007-2018. Health behaviors of LE8 including diet, physical activity and tobacco smoke exposure. The outcome was the odd of hypertension in adolescents. The weighted univariate and multivariate logistic regression was unitized to explore the relationship between CVH score and hypertension in adolescents. Subgroup analysis and sensitivity analysis were further conducted to explore the association across different populations. RESULTS: Totally 3,941 adolescents aged 12-17 years were included, with the mean aged of 14.48 ± 0.04 years. Of whom, 203 (5.15%) had hypertension. After adjusted all covariates, high CVH score was associated with the lower odds of hypertension (OR = 0.32, 95%CI: 0.17-0.61), especially in boys (OR = 0.23, 95%CI: 0.11-0.51) and adolescents with overweight/obesity (OR = 0.24, 95%CI: 0.10-0.56). Sensitivity analysis reported that the association between CVH score and the odds of hypertension was also robust after excluding self-reported hypertension and medication taking (OR = 0.37, 95%CI: 0.18-0.74). CONCLUSION: A high CVH score, indicating a greater adherence of health behaviors, was associated with a reduced odds of hypertension, especially among boys and overweight/obesity adolescents. Large-scale prospective cohort studies are needed to further explore the association between health behaviors defined in LE8 and hypertension among adolescents.

Kinesin Family Member-18A (KIF18A) Promotes Cell Proliferation and Metastasis in Hepatocellular Carcinoma.

BACKGROUND & AIMS: Kinesin family member 18A (KIF18A) is notable for its aberrant expression across various cancer types and its pivotal role is driving cancer progression. In this study, we aim to investigate the intricate molecular mechanisms underlying the impact of KIF18A on the progression of HCC. METHODS: Western blotting assays, a quantitative real-time PCR and immunohistochemical analyses were performed to quantitatively assess KIF18A expression in HCC tissues. We then performed genetic manipulations within HCC cells by silencing endogenous KIF18A using short hairpin RNA (shRNA) and introducing exogenous plasmids to overexpress KIF18A. We monitored cell progression, analyzed cell cycle and cell apoptosis and assessed cell migration and invasion both in vitro and in vivo. Moreover, we conducted RNA-sequencing to explore KIF18A-related signaling pathways utilizing Reactome and KEGG enrichment methods and validated these critical mediators in these pathways. RESULTS: Analysis of the TCGA-LIHC database revealed pronounced overexpression of KIF18A in HCC tissues, the finding was subsequently confirmed through the analysis of clinical samples obtained from HCC patients. Notably, silencing KIF18A in cells led to an obvious inhibition of cell proliferation, migration and invasion in vitro. Furthermore, in subcutaneous and orthotopic xenograft models, suppression of KIF18A sgnificantly redudce tumor weight and the number of lung metastatic nodules. Mechanistically, KIF18A appears to facilitate cell proliferation by upregulating MAD2 and CDK1/CyclinB1 expression levels, with the activation of SMAD2/3 signaling contributing to KIF18A-driven metastasis. CONCLUSION: Our study elucidates the molecular mechanism by which KIF18A mediates proliferation and metastasis in HCC cells, offering new insights into potential therapeutic targets.

GWAS determined genetic loci associated with callus induction in oil palm tissue culture.

KEY MESSAGE: GWAS identified six loci at 25 kb downstream of WAK2, a crucial gene for cell wall and callus formation, enabling development of a SNP marker for enhanced callus induction potential. Efficient callus induction is vital for successful oil palm tissue culture, yet identifying genomic loci and markers for early detection of genotypes with high potential of callus induction remains unclear. In this study, immature male inflorescences from 198 oil palm accessions (dura, tenera and pisifera) were used as explants for tissue culture. Callus induction rates were collected at one-, two- and three-months after inoculation (C1, C2 and C3) as phenotypes. Resequencing generated 11,475,258 high quality single nucleotide polymorphisms (SNPs) as genotypes. GWAS was then performed, and correlation analysis revealed a positive association of C1 with both C2 (R = 0.81) and C3 (R = 0.50), indicating that C1 could be used as the major phenotype for callus induction rate. Therefore, only significant SNPs (P ≤ 0.05) in C1 were identified to develop markers for screening individuals with high potential of callus induction. Among 21 significant SNPs in C1, LD block analysis revealed six SNPs on chromosome 12 (Chr12) potentially linked to callus formation. Subsequently, 13 SNP markers were identified from these loci and electrophoresis results showed that marker C-12 at locus Chr12_12704856 can be used effectively to distinguish the GG allele, which showed the highest probability (69%) of callus induction. Furthermore, a rapid SNP variant detection method without electrophoresis was established via qPCR-based melting curve analysis. Our findings facilitated marker-assisted selection for specific palms with high potential of callus induction using immature male inflorescence as explant, aiding ortet palm selection in oil palm tissue culture.

Systematic Chemical Analysis of Crude Glycan Isolates from the Seven-Herb Decoction Quanzhenyiqitang with Anti-COPD Activity.

The classical Chinese Medicine prescription, Quanzhenyiqitang (QZYQT), containing seven tonic herbs (Shudi, Dangshen, Maidong, Baizhu, Niuxi, Fuzi, and Wuweizi) is clinically used to treat chronic obstructive pulmonary disease (COPD). Although there are studies on the pharmacological effects of QZYQT, little attention has been paid to its active carbohydrate ingredients. We performed a systematic chemical analysis of the crude glycan isolates from the seven-herb decoction (GI-QZYQT) after confirming its anti-COPD activity. GI-QZYQT could enhance lung function, reduce lung damage, and alleviate inflammatory response in mice with COPD. Moreover, two monosaccharides (fructose and glucose) and six oligosaccharides (sucrose, melibiose, 1-kestose, raffinose, mannotriose, and stachyose), accounting for 40.23 % of GI-QZYQT, were discovered using hydrophilic interaction liquid chromatography-evaporative light-scattering detection. Inulin-type fructan with an average molecular weight of 2112 Da was identified using high-performance gel-permeation chromatography in combination with monosaccharide mapping analysis, accounting for 20.10 % of GI-QZYQT in mass. The comparison study showed that the identified monosaccharides, oligosaccharides, and the inulin-type fructan of GI-QZYQT were mainly derived from herbs of Shudi, Dangshen, Maidong, Baizhu, and Niuxi. These findings provide crucial information on the chemical composition of GI-QZYQT, which is vital for the in-depth understanding of its bioactivity, mechanism, and product development.

A Subunit-Based Concept for Preoperative Design of the Cauliflower Ear.

PURPOSE: Cauliflower ear is an ear deformity caused by a closed ear injury with varying severity. Several studies on the systematic reconstruction of cauliflower ear have been reported. Here, the authors aim to introduce a simplified subunit-based reconstruction concept for the cauliflower ear. METHODS: The authors retrospectively analyzed all patients who underwent surgery to repair cauliflower ear in our department from April 2021 to April 2023. Patients' demographic information, clinical characteristics, and outcomes were recorded. All patients were followed up for 1 year. TECHNIQUE: The authors assessed each subunit of the cauliflower ear in sequence in terms of the change in size and shape and decided whether tissue removal or grafting is needed. The surgical design was obtained by a combination of all subunits. RESULTS: The authors included a total of 5 patients with mild and moderate cauliflower ear repaired by the subunit-based method. The shape of all the involved ear subunits of our patients was almost restored. No patient needed the use of cartilage grafts and flaps. The authors summarized 5 common subunits with deformity: helix, scaphoid fossa, antihelix crura and triangular fossa, antihelix body, and concha. The pathology results reported a keloid in 1 case. All patients reported no recurrence and were satisfied with the surgery after 1 year. CONCLUSIONS: The authors reported a simplified subunit-based method of preoperative evaluation and design of cauliflower ear, as a new alternative option to complement the current clinical strategies. The authors also reported the first case of a keloid in cauliflower ear.

Theoretical Analysis of Coordination Geometries in Transition Metal-Histidine Complexes Using Quantum Chemical Calculations.

A theoretical investigation utilizing density functional theory (DFT) calculations was conducted to explore the coordination complexes formed between histidine (His) ligands and various divalent transition metal ions (Mn2+, Fe2+, Co2+, Ni2+, Cu2+, and Zn2+). Conformational exploration of the His ligand was initially performed to assess its stability upon coordination. Both 1:1 and 1:2 of metal-to-ligand complexes were scrutinized to elucidate their structural features and the relative stability of the complexes. This study examined the ability of His to act as a bidentate or tridentate coordinating ligand, along with the differences in coordination geometry when solvent effects were incorporated. The reduced density gradient (RDG) analysis and local electron attachment energy (LEAE) analysis were employed to elucidate the interaction planes and the nucleophilic and electrophilic properties. The electronic properties were analyzed through electrostatic potential (ESP) maps and natural population analysis (NPA) of atomic charge distributions. This computational study provides valuable insights into the diverse coordination modes of His and its interactions with divalent transition metal ions, contributing to a better understanding of the role of this amino acid ligand in the formation of transition metal complexes. The findings can aid in the design and construction of self-assembled structures involving His-metal coordination.

Quantum Chemical Investigation into the Structural Analysis and Calculated Raman Spectra of Amylose Modeled with Linked Glucose Molecules.

This study presents a quantum chemical investigation into the structural analysis and calculated Raman spectra of modeled amylose with varying units of linked glucose molecules. We systematically examined the rotation of hydroxymethyl groups and intramolecular hydrogen bonds within these amylose models. Our study found that as the number of linked glucose units increases, the linear structure becomes more complex, resulting in curled, cyclic, or helical structures facilitated by establishing various intramolecular interactions. The hydroxymethyl groups were confirmed to form interactions with oxygen atoms and with hydroxymethyl and hydroxyl groups from adjacent rings in the molecular structures. We identified distinct peaks and selected specific bands applicable in various analytical contexts by comparing their calculated Raman spectra. Representative vibrational modes within selected regions were identified across the different lengths of amylose models, serving as characteristic signatures for linear and more coiled structural conformations. Our findings contribute to a deeper understanding of amylose structures and spectroscopic signatures, with implications for theoretical studies and potential applications. This work provides valuable reference points for the detailed assignment of Raman peaks of amylose structure, facilitating their application in broader research on carbohydrate structures and their associated spectroscopic properties.

Leap-Type Response of Redox/Photo-Active Lanthanide-Based Metal-Organic Frameworks for Early and Accurate Screening of Prostate Cancer.

The development of high-accuracy technologies to distinguish the quite tiny concentration change of tumor markers between negative and positive is of vital significance for early screening and diagnosis of cancers, but is still a great challenge for the conventional biosensors because of their "gradual" detection mode. Herein, a unique "leap-type" responsive lanthanide MOF-based biosensor (designated as Tb-CeMOF-X) with defect-mediated redox-/photo-activities is developed for precisely identifying acid phosphatase (ACP), an early pathological marker of prostate cancer (PCa) in serum. The engineered Tb-CeMOF-X probe achieves a bursting switch-on luminescence at the critical concentration of ACP (9 U ⋅ L-1), while keeping silent below this threshold, undergoing a qualitative signal change from "zero" to "one" between negative and positive indicators and thus significantly improving the identification precision. Significantly, such "leap-type" response performance can be further edited and amplified by rational defect engineering in the crystal structure to improve the accessibility of active centers, consequently maximizing the detection sensitivity toward ACP in the complex biological media. This study proposes the first paradigm for the development of "leap-type" biosensors with ultra-sensitive differentiation capability between negative and positive, and provides a potentially valuable tool for early and accurate screening of PCa.

Self-Assembly of Glycerol-Amphiphilic Janus Dendrimers Amplifies and Indicates Principles for the Selection of Stereochemistry by Biological Membranes.

The principles for the selection of the stereochemistry of phospholipids of biological membranes remain unclear and continue to be debated. Therefore, any new experiments on this topic may help progress in this field. To address this question, three libraries of constitutional isomeric glycerol-amphiphilic Janus dendrimers (JDs) with nonsymmetric homochiral, racemic, and symmetric achiral branching points were synthesized by an orthogonal-modular-convergent methodology. These JDs amplify self-assembly, and therefore, monodisperse vesicles known as dendrimersomes (DSs) with predictable dimensions programmed by JD concentration were assembled by rapid injection of their ethanol solution into water. DSs of homochiral JD enantiomers, racemic, including mixtures of different enantiomers, and achiral exhibited similar DS size-concentration dependence. However, the number of bilayers of DSs assembled from homochiral, achiral, and racemic JDs determined by cryo-TEM were different. Statistical analysis of the number of bilayers and coarse-grained molecular dynamics simulations demonstrated that homochiral JDs formed predominantly unilamellar DSs. Symmetric achiral JDs assembled only unilamellar DSs while racemic JDs favored multilamellar DSs. Since cell membranes are unilamellar, these results indicate a new rationale for nonsymmetric homochiral vs racemic selection. Simultaneously, these experiments imply that the symmetric achiral lipids forming more stable membrane, probably had been the preferable assemblies of prebiotic cell membranes.

Genome-Wide SNP and Indel Discovery in Abaca (Musa textilis Née) and among Other Musa spp. for Abaca Genetic Resources Management.

Abaca (Musa textilis Née) is an economically important fiber crop in the Philippines. Its economic potential, however, is hampered by biotic and abiotic stresses, which are exacerbated by insufficient genomic resources for varietal identification vital for crop improvement. To address these gaps, this study aimed to discover genome-wide polymorphisms among abaca cultivars and other Musa species and analyze their potential as genetic marker resources. This was achieved through whole-genome Illumina resequencing of abaca cultivars and variant calling using BCFtools, followed by genetic diversity and phylogenetic analyses. A total of 20,590,381 high-quality single-nucleotide polymorphisms (SNP) and DNA insertions/deletions (InDels) were mined across 16 abaca cultivars. Filtering based on linkage disequilibrium (LD) yielded 130,768 SNPs and 13,620 InDels, accounting for 0.396 ± 0.106 and 0.431 ± 0.111 of gene diversity across these cultivars. LD-pruned polymorphisms across abaca, M. troglodytarum, M. acuminata and M. balbisiana enabled genetic differentiation within abaca and across the four Musa spp. Phylogenetic analysis revealed the registered varieties Abuab and Inosa to accumulate a significant number of mutations, eliciting further studies linking mutations to their advantageous phenotypes. Overall, this study pioneered in producing marker resources in abaca based on genome-wide polymorphisms vital for varietal authentication and comparative genotyping with the more studied Musa spp.

Quantum Chemical Calculations of Flexible Tripeptide-Ni(II) Ion-Mediated Supramolecular Fragments and Comparative Analysis of Tripeptide Complexes with Various Metal(II) Ions.

An automated conformational search method was employed to efficiently determine the stable conformers and weak hydrogen bonds of a flexible tripeptide coordinated with a solitary metal(II) ion in an aqueous environment. Quantum chemical calculations were performed to investigate the tendency of octahedral coordination formation between different metal(II) ions and various coordination models (ammonia molecule, chelate molecule, and flexible tripeptide). The octahedral coordination was analyzed by decomposing it into tridentate, bidentate, and monodentate coordination model complexes to assess their formation propensities and conformational properties. Additionally, population analysis, including electrostatic potential mapping and natural population analysis, was performed to identify the unique properties of the Ni(II) ion in forming octahedral coordination in crystals and to explore the potential of other metal(II) ions for self-assembling novel coordination configurations in peptide-metal compounds. Two common hydrogen bonding interactions were examined by using artificial forces to facilitate dissociation or reinforcement.

Successful treatment of a severe Takotsubo syndrome case complicated by liver abscess.

The main manifestations of Takotsubo syndrome (TTS) are a spherical expansion of the left ventricle or near the apex and decreased systolic function. TTS is mostly thought to be induced by emotional stress, and the induction of TTS by severe infection is not often reported. A 72-year-old female patient with liver abscess reported herein was admitted due to repeated fever with a history of hypertension and impaired glucose tolerance. Her severe infection caused TTS, and her blood pressure dropped to 80/40 mmHg. IABP treatment was performed immediately and continued for 10 days, and comprehensive medication was administered. Based on her disease course and her smooth recovery, general insights and learnings may be: Adding to mental and other pathological stress reaction, serious infections from pathogenic microorganism could be of great important causation of stress reaction leading to TTS, while basic diseases such as coronary heart disease, hypertension, and diabetes were be of promoting factors; In addition to effective drug therapies for TTS, the importance of the timely using of IABP should be emphasized.

Design, synthesis, and pharmacological evaluation of quinazoline derivatives as novel and potent pan-JAK inhibitors.

Janus kinases (JAKs) play a critical role in modulating the function and expression of inflammatory cytokines related to rheumatoid arthritis (RA). Herein, we report the design, synthesis, and structure-activity relationships (SARs) of a series of novel quinazoline derivatives as JAK inhibitors. Among these inhibitors, compound 11n showed high potency against JAKs (JAK1/JAK2/JAK3/TYK2, IC50 = 0.40, 0.83, 2.10, 1.95 nM), desirable metabolic characters, and excellent pharmacokinetic properties. In collagen-induced arthritis (CIA) models, compound 11n exhibited significant reduction in joint swelling with good safety, which could be served as a potential therapeutic candidate for the treatment of inflammatory diseases.